Role of NRSF/REST in the Regulation of Cardiac Gene Expression and Function

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Alterations in the cardiac gene program affect both cardiac structure and function, and play a key role in the progression of pathological cardiac remodeling and heart failure. For instance, reactivation of fetal cardiac genes in adults is a consistent feature of cardiac hypertrophy and heart failure. Investigation of the transcriptional regulation of cardiac genes revealed a transcriptional repressor, neuron-restrictive silencer factor (NRSF), also called repressor element-1 silencing factor (REST), to be an important regulator of multiple fetal cardiac genes. Inhibition of NRSF in the heart leads to cardiac dysfunction and sudden arrhythmic death accompanied by re-expression of various fetal genes, including those encoding fetal ion channels, such as the HCN channels and T-type Ca2+ channels. These findings shed light on the crucial regulatory function of NRSF in the heart and its importance for maintaining normal cardiac integrity. (Circ J 2013; 77: 2682–2686)
一般社団法人日本循環器学会の論文